Introduction to metabolic regulation

1. Introduction to metabolic regulation Alex Chacon and Jesse Felts 9-30-13

2. Learning Objectives • Introduce energy balance as a key component of homeostasis • Overview the breakdown of energy output and define basal metabolic rate • Discuss hormonal control of energy balance throughout the body • Introduce the thyroid as a regulator of basal metabolic rate (BMR)

3. What is Homeostasis? • The property of a system that regulates its internal environment and tends to maintain a stable, relatively constant set of conditions • pH • Temperature • Solute concentration • Energy balance • Etc.

5. Energy balance in maintaining homeostasis • Weight maintenance • Satiety • Stress control and psychological wellness • Energetic requirement for many cellular functions • ATP, ADP, cAMP, GTP

6. What is energy balance? Input Output

7. Energy imbalance

9. U.S. Department of Health and Human Services

10. Metabolism • The set of life-sustaining chemical transformations within the cells of living organisms • Catabolism – breakdown of organic components (sugar, fat, protein) for the purpose of harvesting energy • Anabolism – synthesis of cellular components such as lipids, proteins, and nucleic acids

11. Metabolism overview

12. Catabolism • Breaks large molecules into small • Polysaccharides, lipids, nucleic acids, proteins  monosaccharides, FAs, nucleotides, amino acids • Degradation of monomers to release energy • Glycolysis, Citric Acid Cycle, Electron Transport Chain  ATP + heat • Gluconeogenesis – breakdown of fat and protein to form glucose • Glycogenolysis – breakdown of glycogen  glucose

14. Anabolism • Constructs large molecules from smaller ones • Often powered by ATP hydrolysis • Simple  complex • Growth and maturation • Ex. bone mineralization • Ex. muscle hypertrophy

17. The Breakdown of Energy Output • TEF – thermic effect of food: energy used in digestion, absorption and distribution of nutrients

18. Basal Metabolic Rate • Energy used by normal cellular process at rest • Breathing, body temperature regulation, cardiac contractions. • 60-70% of your total daily output • Fat is the main energy source burned • 70% of ATP • 30% of ATP is from carbohydrates

19. BMR Breakdown • What organ system uses the most energy in the entire body?

20. BMR varies across individuals • Age: younger people have higher BMRs • Growth: children and pregnant woman have higher BMRs • Cell replication and division • Body composition: lean tissue masshigher BMR • Muscles burn energy even at rest • Maintaining posture and muscle tone

22. How can you control energy balance? • Diet and exercise • “Input” and “output” • Exercise recommendations for adults (CDC): • 150 min/wk of moderate-intensity aerobic activity • Muscle-strengthening activities 2 days/week • Diet: • balance calories with physical activity while maintaining healthy nutrition

25. Calories / Macromolecule • 4 kcal / gram of carbohydrates • 4 kcal / gram protein • 9 kcal / gram fat

26. Energy balance and Disease • There are hundreds of metabolic diseases • Some are more directly related to Energy balance: • Diabetes, hyperthyroidism, hypothyroidism, obesity • What are the three categories of energy output? • What is the biggest one under your control?

27. Obesity Overview • Cause; in general: • Input > output • Diet, Exercise, Genetic susceptibility • Classification

28. Overweight and Obesity • Association of obesity with many other medical conditions1: • Insulin resistance, glucose intolerance, diabetes mellitus, hypertension (high blood pressure), dyslipidemia (high cholesterol), sleep apnea, arthritis, hyperuricemia, gall bladder disease, and certain types of cancer. (Pi-Sunyer 2010) • Leading preventable cause of death worldwide(Barness 2007)

29. Hormonal regulation of energy balance • Biochemical function determined by necessity • May liberate, store, or transform energy containing molecules • Facilitate transport of molecules • Secretion of hormones regulated by feedback mechanisms • Positive feedback - rare • Negative feedback – most common in endocrine systems

30. Cortisol (hydrocortisone) • Stress hormone • Acts systemically • Synthesized by zonafasciulata of adrenal cortex in response to ACTH secretion by the pituitary gland

32. Secretion • Stress induces Corticotropin Releasing Hormone (CRH) released by hypothalamus • Adrenocortropic hormone (ACTH) secreted by pituitary into vascular system • ACTH binding to adrenal cells in zonafasciulata biosynthesis and release of cortisol into vascular system

33. Action • Diverts energy from low priority activities to survive immediate threats (brain activity, etc.) • Increases gluconeogenesis and glycogenolysis in liver • Activates anti-stress and anti-inflammatory pathways • Facilitates the efficacy of epinephrine/NorEp • Counteracts insulin and inhibits peripheral glucose uptake • Shuts down reproductive system • Decreases bone and muscle formation • Heightened in the morning to prepare for a new day

34. Regulation • Increase levels • Prolonged physical and/or mental stress • Burnout • Starvation • Caffeine • Sleep deprivation • Decrease levels • De-stress and de-tox activities • Massage, music, yoga, dancing • Laughing and happiness • Black tea • Fish oil • High levels of cortisol  negative feedback.

36. Epinephrine • “Fight or flight” response • Acts systemically • Hormone AND neurotransmitter synthesized in central nervous system and adrenal medulla from tyrosine and phenylalanine

38. Secretion • Stress induces Sympathetic Nervous System (SNS) activation and ACTH release by the pituitary gland • Preganglionic sympathetic fibers and ACTH stimulate adrenal cells to produce adrenal precursors from tyrosine and phenylalanine • Adrenal enzymes convert precursors  norepinephrine  epinephrine and release from the adrenal glands into the vascular system

39. Action • Prepares the body to expend high amounts of energy in a short period of time • Increases HR, BP, RR • Stimulates glycogenolysis • Triggers lipolysis • Facilitates stronger muscle contraction • Shunts blood and energetic molecules from non-vital tissues

40. Regulation • Cortisol increases epinephrine synthesis from precursors in the adrenal medulla • No feedback mechanism • Action is terminated upon reuptake into nerve terminal endings, dilution, and catabolism by various tissues

42. Thyroid • Intro video: • http://www.youtube.com/watch?v=VCpjv8YcUow

43. Thyroid and Basal Metabolic Rate • Major player in managing metabolism • Hormones: • T3 (triiodothyronine) • T4 (thyroxine) • Calcitonin • Reduces blood Ca2+ • What key element is incorporated in T3 and T4?

44. How do T3 and T4 affect metabolism? • Increase metabolism of proteins and carbohydrates • Increases basal metabolic rate • Other important effects: • Increase heart rate, ventilation rate, increases sympathetic activity, and aids in brain development

45. Thyroid Regulation • Low levels of thyroid hormones • release of thyrotropin-releasing hormone (TRH) by hypothalamus • release of thyroid-stimulating hormone (TSH) by anterior pituitary gland • T3 and T4 produced • Negative feedback loop

47. Thyroid Disorders • Hyperthyroidism • Excess T3 and/or T4 • Every function of the body tends to speed up • Hypothyroidism • Deficiency of T3 and/or T4 • Low metabolism • Most common cause? • Goiter • Swelling of thyroid gland

48. Works Cited • Barness LA, Opitz JM, Gilbert-Barness E (December 2007). "Obesity: genetic, molecular, and environmental aspects". Am. J. Med. Genet. A 143A(24): 3016–34. doi:10.1002/ajmg.a.32035. PMID 18000969. • Forrest D, Visser TJ. 2013. Thyroid Hormone signaling. BiochimBiophysActa. 1830(7):3859. doi: 10.1016/j.bbagen.2013.03.001 • Pi-SunyerFX. Comorbidities of overweight and obesity: current evidence and research issues. St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY 10025, USA. •  "Dietary Guidelines for Americans, 2010." Health.gov.